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Paraoxonase status and plasma butyrylcholinesterase activity in chlorpyrifos manufacturing workers

Journal of Exposure Science & Environmental Epidemiology volume 20, pages 79–89 (2010)Cite this article

Abstract

Chlorpyrifos is an organophosphorus (OP) anticholinesterase insecticide. Paraoxonase (PON1) is an enzyme found in liver and plasma that hydrolyzes a number of OP compounds. PON1 polymorphisms include a glutamine (Q)/arginine (R) substitution at position 192 (PON1Q192R) that affects hydrolysis of OP substrates, with the PON1192Q allotype hydrolyzing chlorpyrifos oxon less efficiently than the PON1192R allotype, a variation potentially important in determining susceptibility to chlorpyrifos. We studied 53 chlorpyrifos workers and 60 referents during 1 year and estimated chlorpyrifos exposure using industrial hygiene and employment records and excretion of the chlorpyrifos metabolite 3,5,6-trichloro-2-pyridinol (TCP). Plasma butyrylcholinesterase (BuChE) activity, which may by inhibited by chlorpyrifos exposure, was measured monthly. In addition, plasma samples were assayed for paraoxonase (PONase), diazoxonase (DZOase), and chlorpyrifosoxonase (CPOase) activity to determine PON1 status (inferred genotypes and their functional activity). Linear regression analyses modeled BuChE activity as a function of chlorpyrifos exposure and covariates. We postulated that the level of CPOase activity and the inferred PON1192 genotype (together reflecting PON1 status) would differ between groups and that PON1 status would modify the models of chlorpyrifos exposure on BuChE activity. Chlorpyrifos workers and referents had a 100-fold difference in cumulative chlorpyrifos exposure. Contrary to our hypotheses, mean CPOase activity was similar in both groups (P=0.58) and PON1192Q showed a slight overrepresentation, not an underrepresentation, in the chlorpyrifos group compared with referents (PON1192QQ, 51% chlorpyrifos, 40% referent; PON192QR, 43% chlorpyrifos, 40% referent; PON192RR, 6% chlorpyrifos, 20% referent, P=0.08). In our models, BuChE activity was significantly inversely associated with measures of interim chlorpyrifos exposure, but the biological effects of chlorpyrifos exposure on BuChE activity were not modified by PON1 inferred genotype or CPOase activity.

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Acknowledgements

We are grateful for assistance from additional investigators on this project, including Richard P Garrison, PhD, Brenda Gillespie, PhD, Bruno Giordani, PhD, Jonathon Raz, PhD (deceased), Sarah S Cohen, C Sima, and other members of the Neurobehavioral Toxicology Program Chlorpyrifos Study team, including Jennifer N Baughman, Nathan Bradshaw, and Zhuolin Li. Clement E Furlong, PhD, Departments of Medicine (Division of Medical Genetics) and Genome Sciences, University of Washington, Seattle, Washington determined the Paraoxonase (PON1) status of the subjects. We also acknowledge the many Dow and Dow AgroSciences employees who assisted at various points in supporting this research. Finally, we are indebted to the Dow employees who volunteered their time as subjects in this study. Portions of this study were presented at the 10th International Symposium on Neurobehavioral Methods and Effects in Environmental and Occupational Health (NEUREOH-2008), Costa Rica, June 11, 2008. The authors certify that all research involving human subjects was done under full compliance with all institutional and national ethical guidelines and with the consent of the subjects. This study was financially supported by Dow AgroSciences, Indianapolis, Indiana, with additional support from The Dow Chemical Company, and Dow Chemical Company Foundation.

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Authors and Affiliations

  1. Department of Neurology, University of Michigan Health System, Ann Arbor, Michigan, USA

    James W Albers

  2. Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA

    David H Garabrant & Rudy J Richardson

  3. Department of Psychiatry (Psychology and Neurobehavioral Toxicology Programs), University of Michigan Health System, Ann Arbor, Michigan, USA

    Stanley Berent

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Correspondence to James W Albers.

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The authors have received research support and at times been retained as consultants or served as expert witnesses in litigation for firms or companies, including Dow and Dow AgroSciences, concerned with the manufacture or use of insecticides. Support of these activities has included both personal and institutional remuneration.

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Albers, J., Garabrant, D., Berent, S. et al. Paraoxonase status and plasma butyrylcholinesterase activity in chlorpyrifos manufacturing workers. J Expo Sci Environ Epidemiol 20, 79–89 (2010). https://doi.org/10.1038/jes.2009.9

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